Notes

Sorption- and diffusion-induced isotopic fractionation inside chloroethenes.
Invivo turnover and invitro pulse-chase studies identified 2 mechanisms contributing to the rapid increase in plasma PCSK9 levels in response to PCSK9i 1) the expected delayed clearance of the antibody-bound PCSK9; and 2) the unexpected post-translational increase in PCSK9 secretion.

PCSK9 re-entry to the liver via LDLR triggers a sensing loop regulating PCSK9 secretion. PCSK9i therapy enhances the secretion of PCSK9, an effect that contributes to the increased plasma PCSK9 levels in treatedsubjects.
PCSK9 re-entry to the liver via LDLR triggers a sensing loop regulating PCSK9 secretion. PCSK9i therapy enhances the secretion of PCSK9, an effect that contributes to the increased plasma PCSK9 levels in treated subjects.
Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown.

This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI).

KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses.

Circulating KBs were high at presentation witients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) a Randomized Controlled Trial; NCT01217307).
Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events.

This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded.

This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 21 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge.

Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5ng/L and the sex-specific 99th percentile) were more likely to have fy those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.
In pulmonary arterial hypertension (PAH), there are no data comparing initial triple oral therapy with initial double oral therapy.

TRITON (The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension; NCT02558231), a multicenter, double-blind, randomized phase 3b study, evaluated initial triple (macitentan, tadalafil, and selexipag) versus initial double (macitentan, tadalafil, and placebo) oral therapy in newly diagnosed, treatment-naive patients with PAH.

Efficacy was assessed until the last patient randomized completed week 26 (end of main observation period). The primary endpoint was change in pulmonary vascular resistance (PVR) at week26.

Patients were assigned to initial triple (n=123) or initial double therapy (n=124). At week 26, both treatment strategies reduced PVR compared with baseline (by 54% and 52%), with no significant difference between groups (ratio of geometric means 0.96; 95% confidence intepoint not met). Exploratory analyses suggested a possible signal for improved long-term outcomes with initial triple versus initial double oral therapy.Transcatheter aortic valve replacement (TAVR) is now the dominant form of aortic valve replacement in the United States. Continued innovation has allowed the technique to be safe and democratized. New advances will increase the number of patients eligible to receive this therapy while increasing safety and efficiency. Herein, the authors review new TAVR technologies, approaches to valve deployment, and dedicated devices for cerebral embolic protection and vascular closure.Transcatheter aortic valve replacement (TAVR) is a standard treatment option for patients with severe aortic stenosis. Management of concomitant coronary artery disease (CAD) in these patients remains controversial with no randomized clinical trials to guide decision making in this cohort. The role of CAD in TAVR has been difficult to evaluate given the current heterogeneity in defining CAD, and the used methods to assess CAD. Subsequently, the role of coronary revascularization remains individualized and assessed on a case-by-case basis by the heart team. In this article, the authors discuss the rationale and prognostic role of CAD in patients undergoing TAVR.The paucity of data regarding the use of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) anatomy due to exclusion from pivotal studies and lack of studies assessing the long-term outcomes and valve performance continue to present a significant challenge as we expand TAVR to patients with BAV anatomy. This article discusses the important anatomic and clinical considerations in the selection and management of patients with BAV with TAVR and reviews the emerging evidence that increasingly suggests this procedure is safe, device success is excellent, and procedural outcomes are improving.All bioprosthetic valves, both surgical and transcatheter, have a finite lifespan before their leaflets inevitably degenerate, leading to stenosis or regurgitation. As younger, low-risk patients receive a transcatheter aortic valve, it is expected that they will most likely outlive their bioprosthetic valve. The heterogeneity of studies regarding surgical valve durability makes the interpretation of the data challenging. Leaflet thickening is seen in transcatheter heart valves but currently there is no evidence that it leads to premature valve deterioration or clinical events. Standardized definitions of structural valve deterioration should allow for comparisons between future clinical trials to assess the durability of different transcatheter heart valves.Transcatheter aortic valve replacement (TAVR) has become the mainstay of treatment for severe symptomatic aortic stenosis. Although many TAVR complication rates including mortality and aortic regurgitation have decreased, stroke rates have remained stable for years. TAVR-related strokes are devastating to patients and their families, and very costly for health care systems. The predictors of stroke in TAVR are not yet well defined, although older age, female gender, carotid and peripheral arterial disease, bicuspid aortic valve anatomy, and atrial fibrillation are emerging as risk factors across studies.Transfemoral is the most widely used access to perform transcatheter aortic valve replacement (TAVR). However, alternative access is needed in up to 21% of patients with TAVR because of a myriad of factors. The authors provide a comprehensive review on alternative access for TAVR, discussing the relevant data and providing the pros and cons of each access route.Approximately 51,000 to 65,000 surgical aortic valve replacement (SAVR) cases are performed in the United States anually. Bioprosthetic degeneration commonly occurs within 10 to 15 years, and nearly 800 redo SAVR cases occur each year. 5-Fluorouracil solubility dmso Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has emerged as a safe and effective alternative, as the Food and Drug Administration approved ViV TAVR with self-expanding transcatheter heart valve in 2015 and balloon-expandable valve in 2017 for failed surgical valves cases at high risk of reoperation. We review ViV TAVR, with specific attention to procedural planning, technical challenges, associated complications, and long-term follow-up.Acute coronary artery occlusion is a rare but devastating complication of transcatheter aortic valve replacement. Coronary obstruction is angiographic evidence of a new-partial or complete-obstruction of a coronary artery. Key factors identifying patients at risk are aortic root anatomy, type of aortic valve, and type of transcatheter heart valve. Techniques to prevent coronary obstruction include intentional leaflet laceration. If acute coronary obstruction does occur, bailout stenting can be challenging and conversion to emergent open heart surgery may be required, both of which are associated with high morbidity and mortality.Mechanical complications after transcatheter aortic valve replacement are fortunately rare with the current generation of devices. Unfortunately, life-threatening complications will occur and it is the responsibility of operators to be familiar with strategies to prevent and manage these challenging scenarios. Because these cases will not occur often, it is important for us to highlight and talk about those that do occur, to learn best practices in how to manage and prevent them going forward. We can learn much from each other's good crash landings.Conduction disturbances (CDs) after transcatheter artic replacement remain a clinical concern and relatively common complication. A recent meta-analysis showed both new-onset persistent left bundle branch block and new permanent pacemaker implantation were related to all-cause death with risk ratio 1.32 (95% confidence interval [CI] 1.17 to 1.49; P less then .001) and 1.17 (95% CI 1.11-1.25; P less then .001) at 1 year, respectively. Preprocedural computed tomography imaging can highlight potential risk factors for CDs, such as membranous septum length, device landing zone calcium, and the annulus size/degree of device oversizing.The self-expanding transcatheter heart valve (Medtronic Cardiovascular Corevalve and Evolut) is a supra-annular, trileafet porcine pericardial valves on a diamond lattice nickel-titanium alloy frame. The TAVR device has undergone significant improvements in design and procedural techniques to further increase safety, efficacy, and durability since they it was first released. Unique design characteristics, as well as patient and procedural factors, favor self-expanding over balloon-expandable prostheses in certain situations. The self-expanding transcatheter heart valve has proven to be an excellent option for severe aortic stenosis patients with any level of surgical risk and preliminary data suggest a comparable durability to surgical tissue valves.
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